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210  structures 751  species 11  interactions 36319  sequences 487  architectures

Family: Homeobox (PF00046)

Summary: Homeobox domain

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This is the Wikipedia entry entitled "Homeobox". More...

Homeobox Edit Wikipedia article

Homeodomain
Homeodomain-dna-1ahd.png
The Antennapedia homeodomain protein from Drosophila melanogaster bound to a fragment of DNA.[1] The recognition helix and unstructured N-terminus are bound in the major and minor grooves respectively.
Identifiers
Symbol Homeodomain
Pfam PF00046
Pfam clan CL0123
InterPro IPR001356
SMART SM00389
PROSITE PDOC00027
SCOP 1ahd
SUPERFAMILY 1ahd

A homeobox is a DNA sequence, around 180 base pairs long, found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis) in animals, fungi and plants. These genes encode homeodomain protein products that are transcription factors sharing a characteristic protein fold structure that binds DNA.[2][3][4] The "homeo-" prefix in the words "homeobox" and "homeodomain" stems from the mutational phenotype known as "homeosis", which is frequently observed when these genes are mutated in animals. Homeosis is a term coined by William Bateson to describe the outright replacement of a discrete body part with another body part. Homeobox genes are not only found in animals, but have also been found in fungi, for example the unicellular yeasts, in plants, and numerous single cell eukaryotes [4].


Discovery

Homeoboxes were discovered independently in 1983 by Ernst Hafen, Michael Levine, and William McGinnis working in the lab of Walter Jakob Gehring at the University of Basel, Switzerland; and by Matthew P. Scott and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington.[5][6] The existence of homeobox genes were first discovered in Drosophila, where mutations in homeobox genes caused the radical alterations known as "homeotic transformations". One of the most famous such mutation is antennapedia, in which legs grow from the head of a fly instead of the expected antennae.

Homeodomain proteins

A homeobox is about 180 DNA base pairs long and encodes a protein domain that binds DNA. The following shows the consensus homeodomain (~60 amino acid residue chain):[7]

            Helix 1          Helix 2         Helix 3/4
         ______________    __________    _________________
RRRKRTAYTRYQLLELEKEFLFNRYLTRRRRIELAHSLNLTERHIKIWFQNRRMKWKKEN
....|....|....|....|....|....|....|....|....|....|....|....|
         10        20        30        40        50        60

Structure

The characteristic homeodomain protein fold consists of a 60-amino acid long domain composed of three alpha helixes. Helix 2 and helix 3 form a so-called helix-turn-helix (HTH) structure, where the two alpha helices are connected by a short loop region. The N-terminal two helices of the homeodomain are antiparallel and the longer C-terminal helix is roughly perpendicular to the axes established by the first two. It is this third helix that interacts directly with DNA via a number of hydrogen bonds and hydrophobic interactions, as well as indirect interactions via water molecules, which occur between specific side chains and the exposed bases within the major groove of the DNA.[8]

Homeodomain proteins are found in eukaryotes [4]. Through the HTH motif, they share limited sequence similarity and structural similarity to prokaryotic transcripiton factors, [9] such as lambda phage proteins that alter the expression of genes in prokaryotes. The HTH motif shows some sequence similarity but a similar structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeodomain proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, whereas for many of the homeotic and other DNA-binding proteins the requirement is relaxed.

Sequence specificity

Homeodomains can bind both specifically and nonspecifically to B-DNA with the C-terminal recognition helix aligning in the DNA's major groove and the unstructured peptide "tail" at the N-terminus aligning in the minor groove. The recognition helix and the inter-helix loops are rich in arginine and lysine residues, which form hydrogen bonds to the DNA backbone; conserved hydrophobic residues in the center of the recognition helix aid in stabilizing the helix packing. Homeodomain proteins show a preference for the DNA sequence 5'-ATTA-3'; sequence-independent binding occurs with significantly lower affinity.

Biological function

Through the DNA-recognition properties of the homeodomain, homeoproteins are believed to regulate the expression of targeted genes and direct the formation of many body structures during early embryonic development.[10] Many homeodomain proteins induce cellular differentiation by initiating the cascades of coregulated genes required to produce individual tissues and organs. Other proteins in the family, such as NANOG are involved in maintaining pluripotency. Homeobox genes are critical in the establishment of body axes during embryogenesis.

Homeoprotein transcription factors typically switch on cascades of other genes. The homeodomain binds DNA in a sequence-specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors. Such complexes have a much higher target specificity than a single homeodomain protein. Homeodomains are encoded both by genes of the Hox gene clusters and by other genes throughout the genome.

The homeobox domain was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates.[2][8][11]

Specific members of the Hox family have been implicated in vascular remodeling, angiogenesis, and disease by orchestrating changes in matrix degradation, integrins, and components of the ECM.[12] HoxA5 is implicated in atherosclerosis.[13][14] HoxD3 and HoxB3 are proinvasive, angiogenic genes that upregulate b3 and a5 integrins and Efna1 in ECs, respectively.[15][16][17][18] HoxA3 induces endothelial cell (EC) migration by upregulating MMP14 and uPAR. Conversely, HoxD10 and HoxA5 have the opposite effect of suppressing EC migration and angiogenesis, and stabilizing adherens junctions by upregulating TIMP1/downregulating uPAR and MMP14, and by upregulating Tsp2/downregulating VEGFR2, Efna1, Hif1alpha and COX-2, respectively.[19][20] HoxA5 also upregulates the tumor suppressor p53 and Akt1 by downregulation of PTEN.[21] Suppression of HoxA5 has been shown to attenuate hemangioma growth.[22] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.[22] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFalpha-inducible monocyte binding to HUVECs.[23][24][25]

Plant homeobox genes

As in animals, the plant homeobox genes code for the typical 60 amino acid long DNA-binding homeodomain or in case of the TALE (three amino acid loop extension) homeobox genes for an "atypical" homeodomain consisting of 63 amino acids. According to their conserved intron–exon structure and to unique codomain architectures they have been grouped into 14 distinct classes: HD-ZIP I to IV, BEL, KNOX, PLINC, WOX, PHD, DDT, NDX, LD, SAWADEE and PINTOX.[26] Conservation of codomains suggests a common eukaryotic ancestry for TALE[27] and non-TALE homeodomain proteins.[28]

POU genes

Proteins containing a POU region consist of a homeodomain and a separate, structurally homologous POU domain that contains two helix-turn-helix motifs and also binds DNA. The two domains are linked by a flexible loop that is long enough to stretch around the DNA helix, allowing the two domains to bind on opposite sides of the target DNA, collectively covering an eight-base segment with consensus sequence 5'-ATGCAAAT-3'. The individual domains of POU proteins bind DNA only weakly, but have strong sequence-specific affinity when linked. The POU domain itself has significant structural similarity with repressors expressed in bacteriophages, particularly lambda phage.

In humans, the POU genes are HDX; POU1F1; POU2F1; POU2F2; POU2F3; POU3F1; POU3F2; POU3F3; POU3F4; POU4F1; POU4F2; POU4F3; POU5F1; POU5F1P1; POU5F1P4; POU5F2; POU6F1; and POU6F2.

Hox genes

Hox gene expression in Drosophila melanogaster.

Hox genes are a subset of homeobox genes. They are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis.[29] The first vertebrate Hox gene was isolated in Xenopus by Eddy De Robertis and colleagues in 1984, marking the beginning of the young science of evolutionary developmental biology ("evo-devo").[30]

In vertebrates, the four paralog clusters are partially redundant in function, but have also acquired several derived functions. In particular, HoxA and HoxD specify segment identity along the limb axis.[citation needed]

The main interest in this set of genes stems from their unique behaviour. They are typically found in an organized cluster. The linear order of the genes within a cluster is directly correlated to the order of the regions they affect as well as the timing in which they are affected. This phenomenon is called colinearity. Due to this linear relationship, changes in the gene cluster due to mutations generally result in similar changes in the affected regions.[citation needed]

For example, when one gene is lost the segment develops into a more anterior one, while a mutation that leads to a gain of function causes a segment to develop into a more posterior one. This is called ectopia. Famous examples are Antennapedia and bithorax in Drosophila, which can cause the development of legs instead of antennae and the development of a duplicated thorax, respectively.[citation needed]

Molecular evidence shows that some limited number of Hox genes have existed in the Cnidaria since before the earliest true Bilatera, making these genes pre-Paleozoic.[31]

Human homeobox genes

The Hox genes in humans are organized in four chromosomal clusters:

name chromosome gene
HOXA (or sometimes HOX1) - HOXA@ chromosome 7 HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11, HOXA13
HOXB - HOXB@ chromosome 17 HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXB7, HOXB8, HOXB9, HOXB13
HOXC - HOXC@ chromosome 12 HOXC4, HOXC5, HOXC6, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12, HOXC13
HOXD - HOXD@ chromosome 2 HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13

Humans have a "distal-less homeobox" family: DLX1, DLX2, DLX3, DLX4, DLX5, and DLX6. Dlx genes are involved in the development of the nervous system and of limbs.[32]

Human TALE (Three Amino acid Loop Extension) homeobox genes for an "atypical" homeodomain consist of 63 rather than 60 amino acids. IRX1; IRX2; IRX3; IRX4; IRX5; IRX6; MEIS1; MEIS2; MEIS3; MKX; PBX1; PBX2; PBX3; PBX4; PKNOX1; PKNOX2;

In addition, humans have the following homeobox genes and proteins:

Mutations

Mutations to homeobox genes can produce easily visible phenotypic changes.

Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be (antennapedia), and a second pair of wings.

Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution of segmented animals. However, Hox genes typically determine the identity of body segments.

Interestingly, there is one insect family, the xyelid sawflies, in which both the antennae and mouthparts are remarkably leg-like in structure. This is not uncommon in arthropods as all arthropod appendages are homologous.

Regulation

Hox genes and their associated microRNAs are highly conserved developmental master regulators with tight tissue-specific, spatiotemporal control. These genes are known to be dysregulated in several cancers and are often controlled by DNA methylation.[13][33] The regulation of Hox genes is highly complex and involves reciprocal interactions, mostly inhibitory. Drosophila is known to use the Polycomb and Trithorax Complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. Polycomb-group proteins can silence the HOX genes by modulation of chromatin structure.[34]

See also

References

  1. ^ PDB: 1AHD​; Billeter M, Qian YQ, Otting G, Müller M, Gehring W, Wüthrich K (Dec 1993). "Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex". Journal of Molecular Biology. 234 (4): 1084–93. PMID 7903398. doi:10.1006/jmbi.1993.1661. 
  2. ^ a b Gehring WJ (Aug 1992). "The homeobox in perspective". Trends in Biochemical Sciences. 17 (8): 277–80. PMID 1357790. doi:10.1016/0968-0004(92)90434-B. 
  3. ^ Gehring WJ (Dec 1993). "Exploring the homeobox". Gene. 135 (1–2): 215–21. PMID 7903947. doi:10.1016/0378-1119(93)90068-E. 
  4. ^ a b c Bürglin, TR, Affolter, M (Oct 2015). "Homeodomain proteins: an update". Chromosoma. 125 (3): 1–25. PMC 4901127Freely accessible. PMID 26464018. doi:10.1007/s00412-015-0543-8. 
  5. ^ McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ (1984). "A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes". Nature. 308 (5958): 428–33. PMID 6323992. doi:10.1038/308428a0. 
  6. ^ Scott MP, Weiner AJ (Jul 1984). "Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila". Proceedings of the National Academy of Sciences of the United States of America. 81 (13): 4115–9. PMC 345379Freely accessible. PMID 6330741. doi:10.1073/pnas.81.13.4115. 
  7. ^ Bürglin TR. "The homeobox page" (gif). Karolinksa Institute. 
  8. ^ a b Schofield PN (1987). "Patterns, puzzles and paradigms - The riddle of the homeobox". Trends Neurosci. 10: 3–6. doi:10.1016/0166-2236(87)90113-5. 
  9. ^ http://www.cathdb.info/version/v4_0_0/superfamily/1.10.10.60
  10. ^ Corsetti MT, Briata P, Sanseverino L, Daga A, Airoldi I, Simeone A, Palmisano G, Angelini C, Boncinelli E, Corte G (Sep 1992). "Differential DNA binding properties of three human homeodomain proteins". Nucleic Acids Research. 20 (17): 4465–72. PMC 334173Freely accessible. PMID 1357628. doi:10.1093/nar/20.17.4465. 
  11. ^ Scott MP, Tamkun JW, Hartzell GW (Jul 1989). "The structure and function of the homeodomain". Biochimica et Biophysica Acta. 989 (1): 25–48. PMID 2568852. doi:10.1016/0304-419x(89)90033-4. 
  12. ^ Gorski DH, Walsh K (Nov 2000). "The role of homeobox genes in vascular remodeling and angiogenesis". Circulation Research. 87 (10): 865–72. PMID 11073881. doi:10.1161/01.res.87.10.865. 
  13. ^ a b Dunn J, Thabet S, Jo H (Jul 2015). "Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and Atherosclerosis". Arteriosclerosis, Thrombosis, and Vascular Biology. 35 (7): 1562–9. PMC 4754957Freely accessible. PMID 25953647. doi:10.1161/ATVBAHA.115.305042. 
  14. ^ Dunn J, Simmons R, Thabet S, Jo H (Oct 2015). "The role of epigenetics in the endothelial cell shear stress response and atherosclerosis". The International Journal of Biochemistry & Cell Biology. 67: 167–76. PMC 4592147Freely accessible. PMID 25979369. doi:10.1016/j.biocel.2015.05.001. 
  15. ^ Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh DA (Oct 1997). "Induction of the angiogenic phenotype by Hox D3". The Journal of Cell Biology. 139 (1): 257–64. PMC 2139816Freely accessible. PMID 9314544. doi:10.1083/jcb.139.1.257. 
  16. ^ Boudreau NJ, Varner JA (Feb 2004). "The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis". The Journal of Biological Chemistry. 279 (6): 4862–8. PMID 14610084. doi:10.1074/jbc.M305190200. 
  17. ^ Myers C, Charboneau A, Boudreau N (Jan 2000). "Homeobox B3 promotes capillary morphogenesis and angiogenesis". The Journal of Cell Biology. 148 (2): 343–51. PMC 2174277Freely accessible. PMID 10648567. doi:10.1083/jcb.148.2.343. 
  18. ^ Chen Y, Xu B, Arderiu G, Hashimoto T, Young WL, Boudreau N, Yang GY (Nov 2004). "Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice". Journal of Cerebral Blood Flow and Metabolism. 24 (11): 1280–7. PMID 15545924. doi:10.1097/01.WCB.0000141770.09022.AB. 
  19. ^ Myers C, Charboneau A, Cheung I, Hanks D, Boudreau N (Dec 2002). "Sustained expression of homeobox D10 inhibits angiogenesis". The American Journal of Pathology. 161 (6): 2099–109. PMC 1850921Freely accessible. PMID 12466126. doi:10.1016/S0002-9440(10)64488-4. 
  20. ^ Mace KA, Hansen SL, Myers C, Young DM, Boudreau N (Jun 2005). "HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair". Journal of Cell Science. 118 (Pt 12): 2567–77. PMID 15914537. doi:10.1242/jcs.02399. 
  21. ^ Rhoads K, Arderiu G, Charboneau A, Hansen SL, Hoffman W, Boudreau N (2005). "A role for Hox A5 in regulating angiogenesis and vascular patterning". Lymphatic Research and Biology. 3 (4): 240–52. PMID 16379594. doi:10.1089/lrb.2005.3.240. 
  22. ^ a b Arderiu G, Cuevas I, Chen A, Carrio M, East L, Boudreau NJ. "HoxA5 stabilizes adherens junctions via increased Akt1". Cell Adhesion & Migration. 1 (4): 185–95. PMC 2634105Freely accessible. PMID 19262140. doi:10.4161/cam.1.4.5448. 
  23. ^ Zhu Y, Cuevas IC, Gabriel RA, Su H, Nishimura S, Gao P, Fields A, Hao Q, Young WL, Yang GY, Boudreau NJ (Jun 2009). "Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain". Journal of Neuropathology and Experimental Neurology. 68 (6): 626–32. PMC 2728585Freely accessible. PMID 19458547. doi:10.1097/NEN.0b013e3181a491ce. 
  24. ^ Chen H, Rubin E, Zhang H, Chung S, Jie CC, Garrett E, Biswal S, Sukumar S (May 2005). "Identification of transcriptional targets of HOXA5". The Journal of Biological Chemistry. 280 (19): 19373–80. PMID 15757903. doi:10.1074/jbc.M413528200. 
  25. ^ Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH (Jul 2011). "Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation". Biochemical and Biophysical Research Communications. 410 (2): 312–6. PMID 21664342. doi:10.1016/j.bbrc.2011.05.139. 
  26. ^ Mukherjee K, Brocchieri L, Bürglin TR (Dec 2009). "A comprehensive classification and evolutionary analysis of plant homeobox genes". Molecular Biology and Evolution. 26 (12): 2775–94. PMC 2775110Freely accessible. PMID 19734295. doi:10.1093/molbev/msp201. 
  27. ^ Bürglin TR (Nov 1997). "Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals". Nucleic Acids Research. 25 (21): 4173–80. PMC 147054Freely accessible. PMID 9336443. doi:10.1093/nar/25.21.4173. 
  28. ^ Derelle R, Lopez P, Le Guyader H, Manuel M (2007). "Homeodomain proteins belong to the ancestral molecular toolkit of eukaryotes". Evolution & Development. 9 (3): 212–9. PMID 17501745. doi:10.1111/j.1525-142X.2007.00153.x. 
  29. ^ Alonso CR (Nov 2002). "Hox proteins: sculpting body parts by activating localized cell death". Current Biology. 12 (22): R776–8. PMID 12445403. doi:10.1016/S0960-9822(02)01291-5. 
  30. ^ Carrasco AE, McGinnis W, Gehring WJ, De Robertis EM (Jun 1984). "Cloning of an X. laevis gene expressed during early embryogenesis coding for a peptide region homologous to Drosophila homeotic genes". Cell. 37 (2): 409–14. PMID 6327066. doi:10.1016/0092-8674(84)90371-4. 
  31. ^ Ryan JF, Mazza ME, Pang K, Matus DQ, Baxevanis AD, Martindale MQ, Finnerty JR (2007). "Pre-bilaterian origins of the Hox cluster and the Hox code: evidence from the sea anemone, Nematostella vectensis". PLOS ONE. 2 (1): e153. PMC 1779807Freely accessible. PMID 17252055. doi:10.1371/journal.pone.0000153. 
  32. ^ Kraus P, Lufkin T (Jul 2006). "Dlx homeobox gene control of mammalian limb and craniofacial development". American Journal of Medical Genetics Part A. 140 (13): 1366–74. PMID 16688724. doi:10.1002/ajmg.a.31252. 
  33. ^ Bhatlekar S, Fields JZ, Boman BM (Aug 2014). "HOX genes and their role in the development of human cancers". Journal of Molecular Medicine. 92 (8): 811–23. PMID 24996520. doi:10.1007/s00109-014-1181-y. 
  34. ^ Portoso M, Cavalli G (2008). "The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming". RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press. ISBN 978-1-904455-25-7. 

Further reading

  • Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky L, Darnell J (2003). Molecular Cell Biology (5th ed.). New York: W.H. Freeman and Company. ISBN 978-0-7167-4366-8. 
  • Tooze C, Branden J (1999). Introduction to protein structure (2nd ed.). New York: Garland Pub. pp. 159–66. ISBN 978-0-8153-2305-1. 
  • Ogishima S, Tanaka H (Jan 2007). "Missing link in the evolution of Hox clusters". Gene. 387 (1–2): 21–30. PMID 17098381. doi:10.1016/j.gene.2006.08.011. 

External links

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Literature references

  1. Gehring WJ; , Trends Biochem Sci 1992;17:277-280.: The homeobox in perspective. PUBMED:1357790 EPMC:1357790


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001356

The homeobox domain or homeodomain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates [PUBMED:2568852, PUBMED:1357790]. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies [PUBMED:12445403]. The domain binds DNA through a helix-turn-helix (HTH) structure. The HTH motif is characterised by two alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure.

The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 256 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like Arg_repressor ARID B-block_TFIIIC Bac_DnaA_C BetR Bot1p BrkDBD C_LFY_FLO Cdc6_C CENP-B_N Cro Crp CSN8_PSD8_EIF3K Cullin_Nedd8 CUT DDRGK DEP Dimerisation Dimerisation2 DsrD DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4447 DUF480 DUF722 DUF739 DUF742 DUF977 E2F_TDP EAP30 ELL ESCRT-II Ets Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_C FokI_N Forkhead Ftsk_gamma FUR GcrA GerE GntR HARE-HTH HemN_C HNF-1_N Homeobox Homeobox_KN Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_5 HTH_6 HTH_7 HTH_8 HTH_9 HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MarR MarR_2 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 Mor MotA_activ MqsA_antitoxin MRP-L20 Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NUMOD1 OST-HTH P22_Cro PaaX PadR PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_rep_org_N Phage_terminase Pou Pox_D5 PuR_N Put_DNA-bind_N Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RP-C RPA RPA_C RQC Rrf2 RTP RuvB_C SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SLIDE SMC_ScpB SpoIIID STN1_2 Sulfolobus_pRN SWIRM TBPIP Terminase_5 TetR_N TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB Trp_repressor UPF0122 Vir_act_alpha_C YdaS_antitoxin YjcQ YokU z-alpha

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(157)
Full
(36319)
Representative proteomes UniProt
(60461)
NCBI
(114048)
Meta
(25)
RP15
(8225)
RP35
(16586)
RP55
(27766)
RP75
(34222)
Jalview View  View  View  View  View  View  View  View  View 
HTML View                 
PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(157)
Full
(36319)
Representative proteomes UniProt
(60461)
NCBI
(114048)
Meta
(25)
RP15
(8225)
RP35
(16586)
RP55
(27766)
RP75
(34222)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(157)
Full
(36319)
Representative proteomes UniProt
(60461)
NCBI
(114048)
Meta
(25)
RP15
(8225)
RP35
(16586)
RP55
(27766)
RP75
(34222)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Unknown
Previous IDs: homeobox;
Type: Domain
Author: Eddy SR
Number in seed: 157
Number in full: 36319
Average length of the domain: 56.00 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 14.83 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 57
Family (HMM) version: 28
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 11 interactions for this family. More...

HNF-1_N Pou Engrail_1_C_sig PD-C2-AF1 SRF-TF Homeobox CUT SBP_bac_1 Pou Geminin HNF-1_N

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Homeobox domain has been found. There are 210 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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